The etiology of a major segment of acute respiratory tract disease, and the mechanism of complications, remain undefined despite technologic advances of the past 2 decades. Certain respiratory disease syndromes in animals and birds have been shown to depend on interacting infectious agents, rather than single pathogens. In human disease there has been no direct demonstration of similar microbial interaction, although the existence of etiologic complexes has been suspected through analogy with the animal diseases and limited epidemiologic observations. It is proposed that examination be made of the role of diverse microbial agents (bacteria, viruses, and mycoplasmas), acting in concert or sequentially, in the etiology of human respiratory tract illnesses and their complications. The study is being performed on natural respiratory disease in a longitudinal population of infants and children. Pulmonary function studies are being done on etiologically defined microbial infections. The results of these studies may have applications in the diagnosis, treatment and prevention of man's most common infectious disease.